Updates on thrombotic thrombocytopenic purpura: Recent developments in pathogenesis, treatment and survivorship

Abstract

Thrombotic microangiopathies (TMAs) represent a heterogeneous group of entities characterized by the same phenotype: microangiopathic hemolytic anemia, thrombocytopenia, and organ damage. Over the last decades, two major syndromes with distinct pathophysiology have been recognized: thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). A severe deficiency of the ADAMTS13 (A Disintegrin And Metalloproteinase with ThromboSpondin type 1 motifs, member 13) enzyme has been established as the key feature for TTP. When ultra-large Von Willebrand factor (UL-VWF) multimers are allowed to accumulate due to the lack of ADAMTS13, uncontrolled platelet aggregation and adhesion can occur forming disseminated microthrombi resulting in clinical the clinical syndrome. TTP can be fatal without prompt recognition and treatment. Over time, increasing awareness, improvements in diagnostic techniques, and advances in therapeutics have increased survival rates substantially. Once previously thought to be only an acute illness, long-term complications in survivorship are being described with increasing frequency. As our understanding of this devastating condition has evolved, a need for updates has emerged in this increasingly complex setting. In this review, we summarize novel data regarding the pathophysiology, clinical diagnosis, acute management, long-term follow up and emerging therapies for TTP.

Keywords

• Thrombotic microangiopathy
• Thrombotic thrombocytopenic purpura
• Plasma exchange
• Rituximab
• Caplacizumab
• ADAMTS13